Homogeneous and heterogeneous dynamics in native and denatured bovine serum albumin.

A characteristic property of unfolded and disordered proteins is their high molecular flexibility, which enables the exploration of a large conformational space. We present neutron scattering experiments on the dynamics of denatured and native folded bovine serum albumin (BSA) in solution. Global protein diffusion and internal macromolecular dynamics were measured using quasielastic neutron time-of-flight and backscattering spectroscopy on the picosecond to nanosecond time- and Ångstrom length-scale. Internal protein dynamics were analysed in a first approach using stretched exponential functions. In denatured BSA predominantly slow heterogeneous dynamics dominates the observed macromolecular motions. Reduction of disulphide bridges in denatured BSA does not significantly alter the visible motions. In native folded BSA fast homogeneous dynamics and slow heterogeneous dynamics were observed. In an alternative data analysis approach, internal protein dynamics was interpreted using the analytical model of the overdamped Brownian oscillator, which allowed us to extract mean square displacements of protein internal dynamics and the fraction of hydrogen atoms participating in the observed motions. Our results demonstrate that denaturation modifies the physical nature of internal protein dynamics significantly as compared to the native folded structure.